Cyclopentanophenanthrene compounds and process



Patented Apr. 29,1954

UNITED ire? omen CYCLOPENTANOPHENANTHRENE CGMBOTUNDS AND mosses George Rosenkranz and Carl lDjerassi, Mexico C ty, Mexico, assignors b0 Syntax S. A., Mexico City, Memco, a corporation of Mexico N0 sawing. Application May 21, 1951,

Serial No. 227,529

5 Claims. (U1. 26i 239.55)

The present invention relates to novel cyclopentanophenanthrene compounds and to a proe= ,ess for the production. thereof.

More particularly the present invention relates to A -steroid trienones provided with the spiroketal side chain at the 16, 1'? position characteristic of the sapogenins and to a novel process for I producing the same. Compounds of the character described are especially useful intermediates, as

for example, as a starting material for hydrogenation studies andalso because these compounds '40 can be readily aromatized with elimination or migration of the angular methyl group to give phenols capable of being degraded into female sex hormones.

There has, therefore, been provided in accordance with the present invention a novel process for the production of A -t1ien-3-one compounds having in the 16, 17 position the spiro- .ketal or similar side chain of the sapogeni'ns There has further been produced in accord- 5,0

ance with the present invention certain novel dibromo intermediate compounds capable of being readily dehydrobrominated to produce the aforementioned A -t'riens as well as a novel process which includes the production of; the 5,5 and aforementioned dibromo compounds and" their dehydrobromination.

The starting materials for the process of the present invention are A -3-ketosapogenin compounds, as for example, A 432-isospirosten-3one, ;69"

2 although other compounds of a similar nature, as for example, the normal 22-spirosten compounds may also be utilized, will be hereinafter set forth. 1 The process of the present invention may be exemplified by the following equation:

CHa

' 5 "In practicing the above process asuitablecompound, which may be characterized by the following general formula, is used:

CH3 CH3 In the foregoing formula Y- is selected from the group consisting of: i

The above compounds are dibrominated as by dissolving the same in a suitable organic solvent, such as----*ethe1:,- at a temperature 'below 15 C., containing-a" few idropsmf hydrogen bromide in acetic acid. The ether solution is then treated dropwise with a solution of bromine (at least 2 mols) in glacial acetic acid. The'reaction' mixture is then allowed to stand in icefOr-a-substantial period of time, as ior example, one-half hour, and the colorless crystals-ofzthe corresponding 2,6-dibromo derivative are then-filtered and washed with ether. Although preferably bromine in ether-acetic acid is utilized for thedibromination, other brominating agents, such as N-bromosuccinimide, may also be utilized. Therclibrom'o derivatives are then dissolved, as for example, in collidine or other suitable .dehydrobrominating agentand refluxedfor approximately. one hour withstirring. I A suitable organic solvent, such as ether, is then added and the collidine is.removed .by washing with dilute aqueous acid and water and the vethersolution.dried and evaporated. The product may then be recrystallized from a suitable solvent, such as acetone, to produce the pure'A -trien. The compounds thus produced, i. e. the dibromo compounds, may be characterized 'by the following general formula:

CH: CH; Y

In the foregoing formula Y is selected from the group consistingof:

The, :noveLtrien compounds-may b characterized by the following generalformula:

CH3 lQH':

In the foregoing formula Y -is selected from the group consistingof:

and

The following specific examples serve to illus- 4 trate but are not intended to limit the present invention:

Ezammeir A solution of 50 g. of A' 22 'isospirosten-3-one 'in 1200 cc. of ice-cold ether containing a few drops of hydrogen bromide acetic acid was "treatedtdropwise with a solution of 38.8 g. of

bromine in 250 cc. of glacial acetic acid. After 'standingfin'iice for "one-half hour the colorless crystals; ofX6=dibromo-A -22-isospirosten-3-one were filtered and washed with ether. The com- ;pounds -had:a;.melting point of 205-20'l C. (with decomposition) (a) 13.9 (chloroform);

ultra-violet absorption maximum at 250 mu.

Example II A solution of 50 g.-'o'f theldibromo derivative of Example I *Was refiux'ed with mechanical stirring for one hour with 300 cc. o'f redistil1ed collidine. After addingether the collidine' was removed by washing well with diluteaqueous acid :and water, dried and evaporated. Several recrystallizations of the residue from acetone afforded pure A fi-22 isospirostatrien-3-one with a melting point of 2ll8-210" C. ((1) -104.5; ultra-violet absorption maximum at 222-256 and 296 mu.

We claim:

1. A new' compound having the following formula: 1 g

GHI

2. A new compound iha ving the renewing formula:

Chi 011; Y

in Yaseccaammas adummsla and I 5 6 3. A new compound consisting of 2,6-dibromowhich comprises dibrominating a compound of A -22-isospirosten-3-one having a melting point the following formula: of 205-207 C. CH3 CH3 4. A new compound consisting of A -22-is0- Q spirostatrien-3-one having a melting point of 5 208-210" C.

5. A process for producing a compound having the following formula:

CH3 CH3 to form the corresponding 2,6-dibromo derivative and thereafter dehydrobrominating the dibromo derivative.

0 15 References Cited in the file of this patent UNITED STATES PATENTS Z/fherem Y is selected from the group consistmg Number Name Date 2,260,328 Miescher Oct. 28, 1941 2,280,828 Inhoffen Apr. 28, 1942 0 2,332,815 Ruzicka Oct. 26, 1943 0 2,340,388 Inhofien Feb. 1, 1944 2,441,560 Buterandt May 18, 1948 and 25 OTHER REFERENCES 0W! Inhofien, Annalen 563, pp. 131-134 (1949). 

1. A NEW COMPOUND HAVING THE FOLLOWING FORMULA: 